A primary aim of the proposed P01 is to develop chronic care treatment for smoking that comprises only experimentally validated intervention components and that is appropriate for every phase of smoking cessation. This will be accomplished using the Multiphase Optimization Strategy (MOST), an engineering inspired methodological framework for developing, optimizing, and evaluating multicomponent treatments. The Design and Optimization Core serves the P01 by providing a centralized resource for expertise and support pertaining to this innovative approach. The Specific Aims are: 1) Support and serve as an intellectual resource for this application of MOST. Throughout the entire funding period it will be necessary to integrate substantive knowledge with specialized methodological expertise on topics such as efficient experimental design, analysis, and decision making based on the results of experimentation. This core will support and help coordinate these activities. 2) Refine the MOST framework and related methodological tools. This P01 application proposes the first comprehensive research program aimed at the principled, systematic optimization of a clinical smoking treatment. The experience gained will advance MOST methods significantly (e.g., by improving methods for selecting intervention components for further study). 3) Disseminate the MOST framework and related methodological tools to the scientific community via journal articles, workshops, and the like to scientists and clinicians, not only in the smoking cessation area but also in other areas of cancer prevention and treatment. 4) In close collaboration with the Analysis Core, conduct secondary data analyses to lay groundwork for a subsequent cycle of MOST to make further incremental improvements to the smoking cessation treatment. Meaningful incremental improvement in effectiveness and/or efficiency is an ongoing objective of MOST. The next cycle of MOST will be proposed in a competitive renewal application. In sum, this core will enable scientific progress to be made simultaneously in both smoking cessation treatment and in methodology for treatment development, with progress in each domain supporting and informing progress in the other.